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Dysregulated autophagy contributes to the abnormal proliferation of trophoblasts, which is closely related to the occurrence of pregnancy\u2010related diseases. Placenta specific 8 (PLAC8, Onzin) is a multifaceted protein proven to promote autophagy and potentiate various tumor progression. Its role in trophoblasts remains elusive. In our present study, PLAC8 expression was detected in tissues of first\u2010trimester placentas (n\u00a0=\u00a05), term placentas (n\u00a0=\u00a05), choriocarcinoma (n\u00a0=\u00a05), and placental site trophoblastic tumor (n\u00a0=\u00a05). PLAC8 expression was increased in gestational neoplasms compared with normal pregnancies. mCherry\u2010EGFP\u2010LC3B reporter and transmission electron microscopy confirmed PLAC8 promoted the autophagic flux of human trophoblast cells. Both gain\u2010of\u2010function and loss\u2010of\u2010function experiments demonstrated PLAC8\u2010regulated autophagy\u2010related genes, including ATG5, ATG12, and Beclin\u20101. In addition, our data showed that PLAC8 co\u2010localized with p53 and promoted its degradation, and p53 re\u2010expression partially abrogated the PLAC8\u2010induced autophagy activity. Furthermore, the overexpression of PLAC8 promoted cell viability and proliferation, acting as a protective mechanism of trophoblasts against the cytotoxicity of etoposide (VP\u201016). Such a phenomenon was effectively abrogated by autophagy inhibitors 3\u2010methyladenine (3\u2010MA) and chloroquine (CQ). In conclusion, PLAC8\u2010induced autophagy to promote the proliferation of trophoblasts. This study provided insights into the mechanism of PLAC8\u2010induced autophagy in trophoblasts, which is significant for a wide range of gestational diseases and may contribute to developing novel treatment strategies for trophoblastic diseases.<\/jats:p>","DOI":"10.1096\/fj.202002075rr","type":"journal-article","created":{"date-parts":[[2021,2,13]],"date-time":"2021-02-13T22:41:26Z","timestamp":1613256086000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["PLAC8 promotes the autophagic activity and improves the growth priority of human trophoblast cells"],"prefix":"10.1096","volume":"35","author":[{"given":"Xuan","family":"Feng","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Obstetrics and Gynecology Hospital Fudan University Shanghai People's Republic of China"},{"name":"Department of Obstetrics and Gynecology of Shanghai Medical School Fudan 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